This proposal has two main objectives: 1) to learn more about the genetic mechanisms that operate in Tetrahymena, both during conjugation and later in the differentiated somatic nucleus and 2) to develop further the utility of Tetrahymena as an experimental model system in cell and molecular biology capable of supporting genetic dissection. The first objective will be important in illuminating remarkable genetic phenomena of general interest related to the elaborate handling of 3 functionally different types of nuclei during conjugation and to the expression, distribution and recombination of somatic (macro-) nuclear genetic information. The second objective is to maximize the efficiency of mutant isolation, genetic analysis and storage of useful clones so that genetic dissection can be used to maximum advantage. The utility of being able to use Tetrahymena for genetic dissection goes beyond the study of Tetrahymena. There are few (if any) other animal cells which combine the facility for doing both genetic and biochemistry which Tetrahymena has. Consequently, this organism has the potential of becoming a model system for animal cells, by providing a versatile experimental system in which problems of general significance to cell biology can be readily approached at the molecular level. Given the universality of the molecular basis of many cellular mechanisms, the concepts and methods derived from this system should have applicability to many health-related problems, such as the biology of eucaryotic disease-causing organisms, developmental problems (cancer and aging, for example) and "molecular" diseases.